Reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods: an open clinical trial

Abstract

Objective: To test the hypothesis that maternal restriction of polyphenolrich foods (PRF), which, like non-steroidal anti-inflammatory drugs (NSAID), inhibit prostaglandin synthesis in the third trimester, reverse fetal ductal constriction (DC). Study Design:An open clinical trial of 51 third trimester fetuses with DC with no history of NSAID intake was designed. All mothers were submitted to a food frequency questionnaire and were oriented to withdrawl PRF, being reassessed after 3 weeks. Doppler parameters were assessed before and after discontinuation of these substances. A control group of 26 third trimester normal fetuses, with no ductus arteriosus (DA) constriction, in which no dietary intervention was offered, was reviewed after 3 weeks. Student's t-test and Wilcoxon's test were used.Result: Mean gestational age was 32±3 weeks (28 to 37 weeks). After discontinuation of PRF (X3 weeks), 48/51 fetuses (96%) showed complete reversal of DC, with decrease in mean ductal systolic velocity (1.74 ± 0.20 m s À1 to 1.31 ± 0.34 m s À1 , P<0.001), mean diastolic velocity (0.33±0.09 m s À1 to 0.21±0.07 m s À1 , P<0.001) and mean right to left ventricular dimension ratio (1.37 ± 0.26 to 1.12 ± 0.17, P<0.001) and increase in mean ductal pulsatility index (PI) (1.98 ± 0.36 to 2.46±0.23, P<0.001). Median daily maternal consumption of PRF was 286 mg per day and decreased after orientation to 0 mg per day, P<0.001. In the control group, with GA of 32±4 w (29-37 w), there was no significant differences in median daily maternal consumption of PRF, mean ductal systolic velocitiy, diastolic velocity, PI and right ventricular to left ventricular diameter ratio (RV/LV) ratio. Keywords: fetal ductal constriction; prostaglandins; pulmonary hypertension; polyphenol-rich foods Introduction Ductal constriction (DC) has long been related to inhibition of the prostaglandin synthesis pathway, mainly as a result of maternal intake of non-steroidal anti-inflammatory drugs (NSAID) in the third trimester of pregnancy. 1-5 Constriction of fetal ductus arteriosus (DA) is a risk factor for pulmonary hypertension in the newborn period, with its known severe consequences. [6][7][8][9][10][11] For several years, many reports have been discussing the high prevalence of DC in the absence of a known trigger effect. 11 It has been discussed that other extrinsic factors, in addition to NSAID, could be involved in the genesis of this important clinical situation. 1,12,13 We and others have already suggested that maternal ingestion of polyphenol-rich foods (PRF) in late pregnancy, such as herbal teas, grape juice, dark chocolate and others, could be associated to fetal DC. [14][15][16][17][18] Experimental studies in fetal lambs have supported this hypothesis, showing a cause and effect relationship of maternal consumption of green tea and other polyphenol-rich substances with constriction of fetal DA in the animal model. 19 In the human setting, we have demonstrated that fetuses exposed to a maternal diet rich in polyphenols in the third trimester show h...

Nitric oxide and reactive species are modulated in the polyphenol-induced ductus arteriosus constriction in pregnant sheep

“…In previous studies from our group, Zielinsky and coworkers demonstrated that the intake of PRF during late pregnancy was able to induce premature DA constriction in human fetuses and recently reported the reversal of ductal constriction after pregnant women were instructed not to consume foods with high polyphenol contents . These findings were corroborated by Kapadia and coworkers, who associated the prenatal DA closure with maternal ingestion of a juice blend containing anthocyanins and proanthocyanidins …”

“…The studies available on the DA dynamics are basically based on the effect of anti‐inflammatory drugs (NSAIDs or glucocorticoids) either in inducing premature DA constriction or in patent ductus arteriosus cases, in which the pharmacological closure of the DA is searched . Therefore, few studies have been conducted with a premature DA constriction without any relation to NSAIDs intake, which are anti‐inflammatory agents, whereas polyphenols in general present simultaneous anti‐inflammatory and antioxidant effects, as shown in our results.…”

Maternal Restriction of Polyphenols and Fetal Ductal Dynamics in Normal Pregnancy: An Open Clinical Trial

“…As mentioned above, this hypothesis was based on knowledge obtained in the past years, and particularly with the demonstration of reversal of the ductal constrictive effects following maternal restriction of polyphenol-rich foods 1 . Ductal constriction is a non-categorical, "yes or no" phenomenon, but rather a continuous spectrum with increasing severity related to the clinical manifestations of right ventricular overload, tricuspid and/or pulmonary regurgitation and Doppler-echocardiographic findings of increased systolic and mainly diastolic ductal flow velocities, as well as decrease of the ductal pulsatility index.…”

“…Recently, we demonstrated that ductal constriction occurring in the absence of maternal intake of anti-inflammatory drugs in the third trimester of pregnancy is reversed by dietary restriction of polyphenol-rich foods, such as herbal teas, mate, coffee, dark chocolate, coffee, from grape, orange, tangerine, red fruits, apple and olive oil 1 . Other clinical and experimental evidences support the association of changes in fetal ductus arteriosus flow and maternal consumption of foods with high concentration of natural anti-inflammatory substances such as polyphenols 2,3 .…”

Conducto arterioso restrictivo tras el consumo de acetaminofén

“…Otros estudios clínicos y experimentales han demostrado que el consumo materno de sustancias ricas en polifenoles, tales como infusiones, zumo de naranja, uva, chocolate y manzana, afectan la hemodinámica normal del conducto arterioso, y por tanto se ha planteado la necesidad de cambiar la orientación de la dieta materna con el objetivo de limitar la ingestión de este tipo de alimentos en el tercer trimestre 9 .…”